Cross-regional dynamics of antibiotic resistance (AR): Genomic evidence of transmission for Escherichia coli carrying last-resort AR gene between food animals and humans in China

The rapidly increasing dissemination of antibiotic-resistant bacteria (ARB) among food animals and humans is a burgeoning public health crisis. Yet, our understanding of ARB transmission is largely constrained to regional studies, with a dearth of insights into cross-regional dynamics. In this study, the whole-genome sequences of >800 <i>E. coli</i> strains harboring last-resort antibiotic resistance genes (LARGs) across 20 regions of China were retrieved from the NCBI RefSeq database. Our analysis uncovered that 1767 human-animal isolate pairs exhibited high homology, with the pairwise average nucleotide identity (ANI) values exceeding 99.5%. By employing phylogenetic analysis, transmission cluster identification, ANI, and single-nucleotide polymorphism (SNP) analysis, 42 human-animal transmission clusters and 306 recent transmission events were identified. Strikingly, more than 90% of these human-animal transmission events (284 out of 306) spanned different regions. Counterfactual analysis indicated that the cross-regional transmission significantly contributes to the prevalence of these ARBs in humans (21.62%), while its role in the food-animal epidemic is less pronounced (3.47%). Our findings underscore the urgency of a more integrated, nationwide approach to address the spread of LARG-harboring bacteria, which is essential to preserving the efficacy of our remaining antibiotic arsenal and safeguarding public health on a global scale.